Out-Law News | 23 Aug 2021 | 2:13 pm | 3 min. read
Personalised treatments manufactured at the point of care in the UK, including cell and gene therapies, would be subject to a bespoke new regulatory framework under plans being developed by the Medicines and Healthcare products Regulatory Agency (MHRA).
The MHRA’s proposals, which are open to consultation until 23 September, concern ‘point of care’ (POC) manufacturing, which encompasses the manufacture of often very innovative and personalised medicinal products and technologies that are supplied within or very close to the healthcare setting.
Participation in the consultation from stakeholders leading the development of POC products will be invaluable to try to ensure that the formal legislative proposals resulting from this consultation remain fit for purpose in the years to come
The MHRA said that while the proposed new regulatory regime for POC products would link in to existing regulatory systems for medicines approvals, clinical trials, evaluation of regulatory compliance at manufacturing sites and safety monitoring, the “standard model” of regulation does not fit with the traits and requirements of POC products.
“A new regulatory framework is being considered to enable the safe development of POC products for supply to patients through clinical trial studies and then on to licensing, i.e. obtain a marketing authorisation underpinned by safety monitoring and minimisation of risks by the Medicines and Healthcare products Regulatory Agency,” the regulator said. “Such a framework requires control measures equivalent to those currently in place for medicinal products to ensure that POC products meet the necessary requirements for quality, safety, and efficacy.”
Life sciences expert Sarah Taylor of Pinsent Masons, the law firm behind Out-Law, said: “The UK is the first country in the world to propose a regulatory framework for POC products. However, it cannot exist in a vacuum. As the MHRA notes, the innovations are not just available in the UK and so equivalent regulatory approaches will be needed in other countries. The MHRA has said that it has initiated discussions with international regulatory partners, and it will be interesting to see how closely any resulting approaches align to ensure that these new products are made available to a wide number of patients.”
One of the traits of POC products are their short shelf-life. The MHRA said the shelf life of POC products can be calculated in “hours, minutes or less”, compared with the two to three years typical of conventional medicinal products. This means that POC products need to be manufactured “in very close proximity to the patient” and “at a large number of sites” rather than at a single manufacturing centre, and that traditional quality control testing and qualified person certification cannot take place prior to their supply. Instead, “control measures” are necessary “at the time of manufacture … to provide assurance of the quality of products followed by a rapid decision to either supply and administer or to reject the product”, according to the regulator.
The MHRA said: “Since most POC products have very short shelf lives they cannot be manufactured in advance or supplied to distant locations, some POC products may be manufactured for an individual patient. These mean that supply has to be by scale-out (i.e. by adding more manufacturing sites) and not scale up (i.e. by adding more capacity to a few existing sites). Experience with POC products in clinical development indicate that some will be manufactured at several hundred UK sites. It follows that inspecting and authorising each manufacturing site and naming all on each product’s marketing authorisation becomes a major and possibly insurmountable issue.”
To address this, the MHRA has proposed a system of regulation for POC products built around a ‘control site’ concept where most of its regulatory focus will be aimed. Under those plans, a single manufacturing site for a manufacturer’s POC products would be named on the clinical trial or marketing authorisation application and be “responsible for overseeing all aspects of the POC manufacturing system including the addition of new manufacturing sites and control of each manufacturing location and their activities”.
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The need for formal legislative proposals is current
The plans under consideration include a potential new system of “local verification” for qualified person certification, while the MHRA said control sites should also be under a requirement to provide assurance that each batch it releases complies with its product specification, though the regulator is also considering accepting product or batch testing post-administration if that is feasible with the individual POC product.
The MHRA’s plans also envisage near- or real-time data exchange between POC sites and the control site.
Examples of POC products cited by the MHRA include advanced therapy medicinal products, such as cell therapy, gene therapy and tissue engineered products, as well as 3D-printed products, blood products and medical gasses.
Taylor said: “Interest and investment in innovative POC products is increasing, and although no POC products have yet sought marketing approval, the MHRA reports that some clinical trials are currently in progress. The MHRA therefore wants to get ahead of the game, and the need for formal legislative proposals is current.” Such proposals are anticipated once feedback from the MHRA’s consultation has been gathered and analysed.
Life sciences expert Tamsin Cornwell, also of Pinsent Masons, said: “The potential therapeutic applications of POC products are extensive and will only increase as technology progresses. The MHRA’s consultation is timely, given that clinical trials for some POC products are in progress, but also foresighted. The consultation notes that the POC framework will need to provide for future product types and references various types of manufacture, such as modular, mobile and home-based manufacture, in addition to POC manufacture, which are expected to increase in use as the range of POC products develops. Participation in the consultation from stakeholders leading the development of POC products will be invaluable to try to ensure that the formal legislative proposals resulting from this consultation remain fit for purpose in the years to come.”